In pre-term infants the development of the retina and retinal vasculature is incomplete at birth and progresses rapidly during the infant?s first few months of life. Many pediatric retinal diseases, including retinopathy of prematurity (ROP), have a vascular etiology and are caused by mal-development of retinal vasculature during this period of rapid growth. Preterm infants at risk for ROP make up 1.4% of the newborn population. Optical coherence tomography (OCT) is a non-invasive imaging modality that can provide micron scale imaging of tissue in vivo. This characteristic has made OCT the gold standard for diagnosis and monitoring of diseases in adult ophthalmology. More recently the development of OCT angiography (OCTA) has led to new insights into diseases such as diabetic retinopathy. However, the OCTA systems used in these studies are large tabletop systems that cannot be readily used to image infants in the neonatal intensive care unit (NICU). In order to bring OCT into the NICU, over the last decade our Duke team has become world leaders in the development and use of handheld optical coherence tomography (HH-OCT) systems. We pioneered the use of HH-OCT in the NICU. Our experience with the use and design of HH-OCT systems have pointed out a glaring need in pediatric ophthalmology. While OCT technology in commercial tabletop systems has progressed rapidly to include new highspeed OCT technologies capable of OCTA, commercial HH-OCT systems still use slower, decade old OCT 32 kHz spectral domain OCT engines. Under previous NIH funding (RO1 EY025009) we have leveraged our expertise in the development of handheld ophthalmic imaging systems to develop a prototype handheld OCT angiography (HH-OCTA) probe based on a 200 kHz OCT engine that has provided initial OCTA images of retinal vascular development and pathology in awake, pre-term infants in the NICU. This Research Project Grant proposal aims to bring together a team of optical engineers and pediatric ophthalmologists with expertise in the design and translation of HH-OCT systems for the purpose of developing significant improvements to the HH-OCTA hardware descried by the following specific aims: Specific aim 1: Development of a high speed, handheld OCTA system with 6-axis motion stabilization: For this proposal we will develop a motion stabilized HH-OCTA system that uses and 800 kHz engine and feedback from an inertial measurement unit to provide 6 axis active compensation of operator hand motion. Specific aim 2: Development of single modality (OCT) retinal tracking and eye motion correction: We will develop new scanning protocols and software that will enable real time detection, removal, and re-scanning of motion artifacts in without the need for scanning laser ophthalmoscope or other similar imaging modality. The expected outcome of this proposal is the design of a highspeed, motion stabilized HH-OCTA system capable of wide field, motion corrected imaging. Given the vascular nature of many pediatric retinal diseases we expect that these images will lead to new insights into the development of the retina in both diseased and normal states.